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Selecting Among First-Line Therapies in CLL: Does Chemoimmunotherapy Still Play a Role?

By: Joseph Cupolo
Posted: Wednesday, December 2, 2020

Anyone treating patients with chronic lymphocytic leukemia (CLL) well knows that the treatment armamentarium has expanded from chemoimmunotherapy to include novel small-molecule inhibitors such as ibrutinib, venetoclax, and acalabrutinib. However, the challenge for many oncologists is whether chemoimmunotherapy still has a role in the first-line setting. During the NCCN 2020 Virtual Annual Conference, Mazyar Shadman, MD, MPH, of the University of Washington, and Deborah M. Stephens, DO, of the University of Utah, offered their expertise on this topic. Highlights of this presentation were published in JNCCN–Journal of the National Comprehensive Cancer Network.

“There is still a role for chemoimmunotherapy,” noted Dr. Shadman. “The advantages include fixed duration of treatment, lack of access to novel agents, and lower cost compared with novel agents. FCR [fludarabine, cyclophosphamide, rituximab] is a reasonable option for young fit patients with mutated IGHV and intact TP53.”

Meanwhile, Dr. Stephens cited several reasons to choose small-molecule inhibitors over chemoimmunotherapy: prolonged progression-free survival and overall survival, a survival benefit maintained in high-risk groups, possible deeper responses when used as earlier-line therapy, and improved quality of life. “Small-molecule inhibitors can improve quality of life,” she stated. “A good example is the RESONATE 2 trial, which showed that…clinically meaningful improvements in multiple quality-of-life domains with ibrutinib compared with chlorambucil were maintained over time, as was improvement in disease-related symptoms.”

In addition, Dr. Stephens stressed that agents such as ibrutinib might be used despite concerns about toxicity. “In choosing front-line therapy in 2020, don’t be distracted by the toxicities of ibrutinib or the fact that ibrutinib and other small- molecule inhibitors are mainly used as continuous therapy. Ibrutinib-related toxicities improve over time. Importantly, the risk of infection with ibrutinib is also reduced over time. Acalabrutinib, approved for CLL in 2019, is a more selective BTK inhibitor than ibrutinib. It is designed to maintain efficacy but with reduced toxicity.”

Disclosures: For presenters’ disclosures, visit jnccn.org.



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